Analysis of amino acid copolymer compositions
AssigneeMomenta Pharmaceutical, Inc.
InventorsYanjie Jiang, Peter James Ahern, James Eric Anderson, Corinne Bauer, Xiangping Zhu, Zachary Shriver
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Abstract
Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard. In some cases, the methods entail treating the co-polymer with pyro-glutamate aminopeptidase to cleave N-terminal pyro-glutamate residues.
Claims49
A method of selecting a batch of a composition comprising an amino acid copolymer, the method comprising:
- providing a batch of a composition comprising an amino acid copolymer;
- measuring the amount of pyro-glutamate (pyro-Glu) in the batch;
- and
- selecting the batch if the amount of pyro-Glu in the batch is within a predetermined range,
- thereby selecting a batch of a composition comprising an amino acid copolymer.
A method of preparing a pharmaceutical composition comprising an amino acid copolymer, the method comprising:
- providing a batch of a composition comprising an amino acid copolymer,
- measuring the amount of pyro-Glu in the batch;
- selecting the batch for use in the preparation of a pharmaceutical composition if the amount of pyro-Glu in the batch is within a predetermined range;
- and
- preparing a pharmaceutical composition comprising at least a portion of the selected batch.
A method of analyzing a composition comprising glatiramer acetate for the presence or amount of pyro-Glu, the method comprising:
- digesting a sample of the composition with a peptidase or protease to generate digestion products,
- evaluating the amount of pyro-Glu in the sample relative to the reference standard by comparing the digestion products to a pyro-Glu reference standard, and
- thereby analyzing a composition comprising glatiramer acetate for the presence or amount of pyro-Glu.
A method for preparing a pharmaceutical composition comprising glatiramer acetate, comprising:
- polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotecting TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of pyro-glutamate (pyro-Glu) in the purified glatiramer acetate.
A method for preparing a pharmaceutical composition comprising glatiramer acetate, comprising:
- polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotecting TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of pyro-glutamate (pyro-Glu) during or after the polymerizing step.
A method for preparing a pharmaceutical composition comprising glatiramer acetate, comprising:
- polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotecting TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of pyro-glutamate (pyro-Glu) during or after the partial depolymerization step.
A method for preparing a pharmaceutical composition comprising glatiramer acetate, comprising:
- polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotecting TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of benzyl alcohol during or after the polymerizing step, wherein the amount of benzyl alcohol is correlated to the amount of pyro-Glu.
A method for preparing a pharmaceutical composition comprising glatiramer acetate, comprising:
- polymerizing N-carboxy anhydrides of L-alanine, benzyl-protected L-glutamic acid, trifluoroacetic acid (TFA) protected L-lysine and L-tyrosine to generate a protected copolymer;
- treating the protected copolymer to partially depolymerize the protected copolymer and deprotect benzyl protected groups and deprotecting TFA-protected lysines to generate glatiramer acetate;
- and purifying the glatiramer acetate,
- wherein the improvement comprises:
- measuring the amount of benzyl alcohol during or after the partial depolymerization step, wherein the amount of benzyl alcohol is correlated to the amount of pyro-Glu.
Dependencies are inferred from the claim text.